title: Prognostic significance of global histone modifications in resected squamous cell carcinoma of the esophagus.
abstract: Patterns of global histone modifications have been recently suggested as outcome predictors in cancer patients. To date, there has been no report on the prognostic significance of global histone modifications in esophageal squamous cell carcinoma. We investigated the role of global histone modification as outcome predictor in patients undergoing esophagectomy for esophageal squamous cell carcinoma. A retrospective clinicopathologic analysis was undertaken of 97 patients with esophageal squamous cell carcinoma who recovered from esophagectomy. Immunohistochemical expression of five histone modification markers, acetylated histone 3 lysine 18 (H3K18Ac), acetylated histone 4 lysine 12 (H4K12Ac), dimethylated histone 4 arginine 3 (H4R3diMe), dimethylated histone 3 lysine 4 (H3 K4diMe), and trimethylated histone 3 lysine 27 (H3K27triMe) was assessed in paraffin-embedded tumor samples. Results were analyzed in relation to patients' clinicopathologic parameters. There was a positive relationship between tumor differentiation and H3K18Ac (P<0.001), H4R3diMe (P=0.003), and H3K27triMe (P<0.001). Expression of H3K27triMe correlated positively with nodal (N) status (P=0.012) and stage (P=0.025). Univariate analysis showed that better survival in patients with low expression of H3K18Ac (P=0.038) and H3K27triMe (P=0.003). Multivariate analysis showed that nodal status, metastasis status (M), and expression of H3K27triMe predicted survival independently (P<0.001, P=0.016, and 0.048, respectively). Low expression of H3K18Ac and H3K27triMe correlated with better prognosis of patients with esophageal squamous cell carcinoma, especially for those of early stages. We hypothesize that expression of H3K27triMe may be considered as a significant survival predictor for patients with esophageal squamous cell carcinoma.
authors.affiliation: Division of Thoracic Surgery, Tri-Service General Hospital, National Defense Medical Center, Taipei, Taiwan. tzao@yahoo.com
authors.forename: Ching
authors.initials: C
authors.lastname: Tzao
authors.forename: Ho-Jui
authors.initials: HJ
authors.lastname: Tung
authors.forename: Jong-Shiaw
authors.initials: JS
authors.lastname: Jin
authors.forename: Guang-Huan
authors.initials: GH
authors.lastname: Sun
authors.forename: Han-Shui
authors.initials: HS
authors.lastname: Hsu
authors.forename: Ban-Hen
authors.initials: BH
authors.lastname: Chen
authors.forename: Cheng-Ping
authors.initials: CP
authors.lastname: Yu
authors.forename: Shih-Chun
authors.initials: SC
authors.lastname: Lee
mesh_terms: D000107:Acetylation; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D014408:Biomarkers, Tumor / Q000032:analysis*; D002294:Carcinoma, Squamous Cell / Q000737:chemistry* / Q000401:mortality / Q000473:pathology / Q000601:surgery; D002454:Cell Differentiation; D004938:Esophageal Neoplasms / Q000737:chemistry* / Q000401:mortality / Q000473:pathology / Q000601:surgery; D016629:Esophagectomy; D005260:Female; D006657:Histones / Q000032:analysis*; D006801:Humans; D007150:Immunohistochemistry; D053208:Kaplan-Meier Estimate; D008207:Lymphatic Metastasis; D008239:Lysine; D008297:Male; D008745:Methylation; D008875:Middle Aged; D009362:Neoplasm Metastasis; D009367:Neoplasm Staging; D011499:Protein Processing, Post-Translational; D012189:Retrospective Studies; D013997:Time Factors; D016896:Treatment Outcome
chemical_list: D014408:Biomarkers, Tumor; D006657:Histones; D008239:Lysine